Faculty Bibliography

Each year, more than 300 million patients worldwide undergo non-cardiac surgery. Perioperative myocardial infarction (MI) is a common cardiovascular complication of surgery; thus, we sought to determine coronary artery anatomy in patients referred for coronary angiography for the evaluation of perioperative MI after non-cardiac surgery.

An unbiased platelet transcriptome profile identified ATP binding cassette subfamily C member 4 (ABCC4) as a novel mediator of platelet activity in virologically suppressed human immunodeficiency virus (HIV)-infected subjects on antiretroviral therapy. Using ex vivo and in vitro cellular and molecular assays we demonstrated that ABCC4 regulated platelet activation by altering granule release and cyclic nucleotide homeostasis through a cAMP-protein kinase A (PKA)-mediated mechanism. Platelet ABCC4 inhibition attenuated platelet activation and effector cell function by reducing the release of inflammatory mediators, such as sphingosine-1-phosphate. ABCC4 inhibition may represent a novel antithrombotic strategy in HIV-infected subjects on antiretroviral therapy.

Patients with peripheral artery disease (PAD) are at heightened risk of cardiovascular morbidity and mortality. We sought to evaluate the risk of concomitant coronary artery disease (CAD) in patients with symptomatic PAD versus PAD without diagnosed CAD, and whether ticagrelor was superior to clopidogrel in reducing that risk. The EUCLID trial randomized 13,885 patients with PAD to antithrombotic monotherapy with ticagrelor or clopidogrel. CAD was defined as prior myocardial infarction (MI), percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG) surgery. Median follow-up was 30 months. Among 4032 (29%) patients with PAD and CAD, 63% had prior MI, 54% prior PCI, and 38% prior CABG. After adjustment for baseline characteristics, patients with PAD and CAD had significantly higher rates of the primary endpoint (cardiovascular death/MI/stroke, 15.3% vs 8.9%, hazard ratio (HR) 1.50, 95% CI: 1.13-1.99; p=0.005), but no statistically significant increase in acute limb ischemia (HR 1.28, 95% CI: 0.57-2.85; p=0.55) or major bleeding (HR 1.10, 95% CI: 0.49-2.48; p=0.81) versus PAD without CAD. Among patients with PAD and CAD, there was no differential treatment effect between ticagrelor versus clopidogrel for the primary efficacy endpoint (HR 1.02, 95% CI: 0.87-1.19; p=0.84), acute limb ischemia (HR 1.03, 95% CI: 0.63-1.69; p=0.89), or major bleeding (HR 1.06, 95% CI: 0.66-1.69; p=0.81). There was a statistically significant interaction between prior coronary stent placement and study treatment ( p=0.03) with a numerical reduction in the primary efficacy endpoint with ticagrelor versus clopidogrel (13.8% vs 16.8%, HR 0.82, 95% CI: 0.65-1.03; p=0.09). Patients with PAD and prior CAD had higher composite rates of cardiovascular death, MI, and ischemic stroke versus PAD without diagnosed CAD. There were no significant differences between ticagrelor and clopidogrel in cardiovascular events or major bleeding. ClinicalTrials.gov Identifier: NCT01732822.

Aim/UNASSIGNED:To investigate the risk of all-cause mortality, recurrent VTE, and hospitalized bleeding in patients with VTE treated with either rivaroxaban or apixaban. Methods and results/UNASSIGNED:Using Danish nationwide registries, patients with VTE treated with rivaroxaban or apixaban in the period from January 1st 2015 to June 30th 2017 were identified. Standardized absolute risks were estimated based on outcome-specific Cox regression models, adjusted for potential confounders. A total of 8,187 patients were included in the study, of which 1,504 (18%) were treated with apixaban (50% males, median age 70 years; inter quartile range (IQR) 56-80) and 6,683 (82%) were treated with rivaroxaban (55% males, median age 67 years; IQR 53-76). The 180 days risk of all-cause mortality was 5.08% (95%CI: 4.08% to 6.08%) in the apixaban group and 4.60% (95% CI: 4.13% to 5.18%) in the rivaroxaban group (absolute risk difference: -0.48% (95% CI: -1.49% to 0.72%) The 180 days risk of recurrent VTE was 2.16% (95%CI: 1.49% to 2.88%) in the apixaban group and 2.22% (95% CI: 1.89% to 2.52%) in the rivaroxaban group (absolute risk difference of 0.06% (95% CI: -0.72% to 0.79%)). The 180 days risk of hospitalized bleeding was 1.73% (95%CI: 1.22% to 2.35%) for patients in the apixaban group and 1.89% (95%CI: 1.56% to 2.20%) in the rivaroxaban group (absolute risk difference: 0.16% (95% CI: -0.59% to 0.81%)). Conclusion/UNASSIGNED:In a nationwide cohort of 8,187 patients with VTE treated with rivaroxaban or apixaban there were no significant differences in the risks of all-cause mortality, recurrent VTE, or hospitalized bleeding.

OBJECTIVES/OBJECTIVE:To investigate temporal trends in the use of non-vitamin K oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) in combination with aspirin and/or clopidogrel in patients with atrial fibrillation (AF) following acute myocardial infarction (MI) and/or percutaneous coronary intervention (PCI). METHODS:Using Danish nationwide registries, all patients with AF who survived 30 days after discharge from MI and/or PCI between 22 August 2011 and 30 September 2016 were identified. RESULTS:-VASc score(congestive heart failure, hypertension, age ≥75 years (2 points), diabetes mellitus, history of stroke/transient ischemic attack/systemic thromboembolism (2 points), vascular disease, age 65-75 years, and female sex) accounted for 132 2814 (95.5%) of patients, and patients with high HAS-BLED score (hypertension, abnormal renal/liver function, history of stroke, history of bleeding, age >65 years, non-steroidal anti-inflammatory drug usages, or alcohol abuse, leaving out labile international normalized ratio (not available), and use of antiplatelets (exposure variable)) accounted for 934 (31.7%) of patients. There was an increase from 10% in 2011 to 52% in 2016 in the use of NOACs in combination with antiplatelet(s). CONCLUSION/CONCLUSIONS:From 2011 to 2016, the use of NOAC in combination with antiplatelet(s) increased in patients with AF following MI/PCI and exceeded the use of VKA in combination with antiplatelet(s) by 2016.

BACKGROUND:Elevated stress is associated with adverse cardiovascular disease outcomes and accounts in part for the poorer recovery experienced by women compared with men after myocardial infarction (MI). Psychosocial interventions improve outcomes overall but are less effective for women than for men with MI, suggesting the need for different approaches. Mindfulness-based cognitive therapy (MBCT) is an evidence-based intervention that targets key psychosocial vulnerabilities in women including rumination (i.e., repetitive negative thinking) and low social support. This article describes the rationale and design of a multicenter randomized controlled trial to test the effects of telephone-delivered MBCT (MBCT-T) in women with MI. METHODS:We plan to randomize 144 women reporting elevated perceived stress at least two months after MI to MBCT-T or enhanced usual care (EUC), which each involve eight weekly telephone sessions. Perceived stress and a set of patient-centered health outcomes and potential mediators will be assessed before and after the 8-week telephone programs and at 6-month follow-up. We will test the hypothesis that MBCT-T will be associated with greater 6-month improvements in perceived stress (primary outcome), disease-specific health status, quality of life, depression and anxiety symptoms, and actigraphy-based sleep quality (secondary outcomes) compared with EUC. Changes in mindfulness, rumination and perceived social support will be evaluated as potential mediators in exploratory analyses. CONCLUSIONS:If found to be effective, this innovative, scalable intervention may be a promising secondary prevention strategy for women with MI experiencing elevated perceived stress.

BACKGROUND AND AIMS/OBJECTIVE:Diabetes mellitus is a coronary heart disease (CHD) risk-equivalent for the outcome of peripheral vascular disease. The impact of diabetes with comorbid risk factors on the outcome of peripheral vascular disease remains unexplored. METHODS:We performed a cross-sectional analysis of participants in Lifeline Vascular Screening Inc. age 40-90 who were screened for peripheral vascular disease, defined as lower extremity peripheral artery disease (PAD, ABI <0.9) and/or carotid artery stenosis (CAS, internal CAS ≥50%). CHD was defined as prior myocardial infarction or revascularization. Risk factors included hypertension, hyperlipidemia, smoking, obesity, sedentary lifestyle and family history of cardiovascular disease. RESULTS:Among 3,517,804 participants, PAD and CAS was identified in 4.4% and 3.7%, respectively. Diabetes was identified in 376,528 participants, 324,680 (86%) of whom did not have CHD. Among diabetic participants without CHD, prevalence of PAD increased with 1-2 (4.3%), 3-4 (7.3%), and ≥5 (12.0%) comorbid risk factors (p trend < 0.0001). The pattern was similar for CAS (3.7%, 6.2%, 8.8%, p trend < 0.0001). Compared to participants without diabetes, those with diabetes and 1-2, 3-4 and ≥5 risk factors had increasing odds of PAD and CAS after adjustment for age, sex and race/ethnicity (1.0, 95% CI 0.98-1.06; 1.8, 95% CI 1.8-1.89; 3.5, 95% CI 3.43-3.64, respectively, p trend < 0.0001). By comparison, in nondiabetic participants, CHD increased odds of PAD and CAS by 2-fold (2.06, 95% CI 2.02-2.1; 2.19, 95% CI 2.15-2.23 respectively). CONCLUSIONS:Diabetes, particularly with comorbid risk factors, confers increased odds of PAD and CAS, even in the absence of CHD. Counseling regarding screening and prevention for peripheral vascular disease among individuals with diabetes and multiple risk factors may be useful.

BACKGROUND:Prior trials comparing a strategy of optimal medical therapy with or without revascularization have not shown that revascularization reduces cardiovascular events in patients with stable ischemic heart disease (SIHD). However, those trials only included participants in whom coronary anatomy was known prior to randomization and did not include sufficient numbers of participants with significant ischemia. It remains unknown whether a routine invasive approach offers incremental value over a conservative approach with catheterization reserved for failure of medical therapy in patients with moderate or severe ischemia. METHODS:The ISCHEMIA trial is a National Heart, Lung, and Blood Institute supported trial, designed to compare an initial invasive or conservative treatment strategy for managing SIHD patients with moderate or severe ischemia on stress testing. Five thousand one-hundred seventy-nine participants have been randomized. Key exclusion criteria included estimated glomerular filtration rate (eGFR) <30 mL/min, recent myocardial infarction (MI), left ventricular ejection fraction <35%, left main stenosis >50%, or unacceptable angina at baseline. Most enrolled participants with normal renal function first underwent blinded coronary computed tomography angiography (CCTA) to exclude those with left main coronary artery disease (CAD) and without obstructive CAD. All randomized participants receive secondary prevention that includes lifestyle advice and pharmacologic interventions referred to as optimal medical therapy (OMT). Participants randomized to the invasive strategy underwent routine cardiac catheterization followed by revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery, when feasible, as selected by the local Heart Team to achieve optimal revascularization. Participants randomized to the conservative strategy undergo cardiac catheterization only for failure of OMT. The primary endpoint is a composite of cardiovascular (CV) death, nonfatal myocardial infarction (MI), hospitalization for unstable angina, hospitalization for heart failure, or resuscitated cardiac arrest. Assuming the primary endpoint will occur in 16% of the conservative group within 4 years, estimated power exceeds 80% to detect an 18.5% reduction in the primary endpoint. Major secondary endpoints include the composite of CV death and nonfatal MI, net clinical benefit (primary and secondary endpoints combined with stroke), angina-related symptoms and disease-specific quality of life, as well as a cost-effectiveness assessment in North American participants. Ancillary studies of patients with advanced chronic kidney disease and those with documented ischemia and non-obstructive coronary artery disease are being conducted concurrently. CONCLUSIONS:ISCHEMIA will provide new scientific evidence regarding whether an invasive management strategy improves clinical outcomes when added to optimal medical therapy in patients with SIHD and moderate or severe ischemia.

Background: Perioperative myocardial infarction (MI) is a common cardiovascular complication of surgery that occurs in up to 5.0% of patients at increased cardiovascular risk. We sought to determine coronary artery anatomy in patients referred for invasive coronary angiography for the evaluation of perioperative MI or myocardial injury after non-cardiac surgery (MINS). Methods: Patients with perioperative MI or MINS who were referred for coronary angiography at NYU Langone Medical Center were retrospectively identified from January 1, 2013 to December 31, 2015. Demographic, clinical, and angiographic characteristics were obtained via electronic medical record review. Results: A total of 31 patients with perioperative MI (n=28) or MINS (n=3) were referred for invasive coronary angiography. The mean age was 70+/-10 years, 52% were male, and cardiovascular risk factors were common (Table). Obstructive coronary artery disease (CAD) was identified in 24 patients (77.4%) and a chronic total occlusion (CTO) of a major epicardial vessel was identified in 11 patients. A total of 15 patients (48.4%) underwent PCI. Among patients without obstructive CAD, angiography revealed mild CAD (stenosis <40% in major epicardial coronary vessels) in the majority (71.4%) of cases. Conclusion: Obstructive CAD is present in the majority of patients with perioperative MI or MINS, with CTO in nearly half of these patients. One-quarter of patients did not have obstructive CAD, and the mechanism of myocardial injury in these patients is unknown. This study reaffirms the benefit of empiric guidelinedirected medical therapy for CAD in patients with perioperative MI or MINS, despite limited evidence from clinical trials in this population